If one doesn't understand the complete biology of disease, aiming at one target requires praying for no collateral damage. - Greg Bennett, CBCD
Rochester, NY (PRWEB) October 20, 2013
The failure of Ariad Pharmaceutical’s leukemia drug, Iclusig is no surprise to the CBCD. If top management at Ariad, and/or their investors, had turned to the CBCD, the Center would have told them that the chance of completing a successful clinical trial was almost zero.
What’s the argument? The productivity crisis in pharmaceutical R&D.
Iclusig was designed to target one specific molecule. However, like every drug, it impacts more than the specific molecule it was designed to target. When a drug impacts the ‘other’ molecules, it causes adverse reactions, or side effects. This was clearly the case in the development of Iclusig because in this case, some of the ‘other’ molecules were actually known.
As the author of an article published in February, 2013 in the formulary management journal P & T wrote, “The primary target (of Iclusig) is Bcr-Abl, an abnormal tyrosine kinase that is expressed in CML and Ph+ ALL (2).” If one carefully notes, however, the drug also “selectively blocks other tyrosine kinases, including FLT3, RET, KIT, and the members of the fibroblast growth factor receptor (FGFR) and platelet-derived growth factor (PDGFR) families (2).”
What kind of adverse reactions resulted from Iclusig’s impact on the ‘other’ molecules?
The answer is frightening. “Serious and fatal cases of arterial thrombosis (the formulation of a blood clot) and liver injury have occurred during treatment… cardiovascular, cerebrovascular, and peripheral vascular thrombosis, including fatal myocardial infarction (MI) (heart attack) and stroke have occurred in treated patients (2).”
In fact, because of these dangerous adverse reactions, “Ariad Pharmaceuticals Inc. abruptly terminated a pivotal clinical trial of its leukemia drug … a move that raised new safety questions and sent the company’s shares plunging more than 40 percent (1).”
Inclusig is another example of the failed “Single Target” paradigm, which is argued to be the underlying cause of the productivity crisis in pharmaceutical R&D. This paradigm is explained in a paper published on March, 2012 in the medical journal Nature Reviews. The paper said that “Much of the pharmaceutical industry's R&D is now based on the idea that high-affinity binding to a single biological target linked to a disease will lead to medical benefit in humans. Indeed, drug-like small molecules tend to bind promiscuously, and this sometimes turns out to have an important role in their efficacy as well as their so-called off-target effects. Targets are parts of complex networks leading to unpredictable effects, and biological systems show a high degree of redundancy, which could blunt the effects of highly targeted drugs (3).”
In simple terms, the idea that a drug binds with only one target is wishful thinking. As it turns out, every drug binds with many targets in the body, the desired one, and many others. Binding to the ‘other’ targets usually causes all the unwanted, surprising, side effects.
"If one doesn’t understand the complete biology of disease, aiming at one target requires praying for no collateral damage. Any drug that passes clinical trials under this paradigm is a miracle. But, miracles are rare, and unpredictable. Investors need to demand a change. They need to put an end to the “Single Target’ paradigm. Otherwise, a successful drug with no side effects will continue to remain elusive." - Greg Bennett, CBCD
In summary, the ‘Single Target’ paradigm pursued by the pharmaceutical industry is a failure. There is a growing need for a different approach.
The CBCD invites scientists, and investors interested in discussing such an approach to contact the Center at: info (at) CBCD (dot) net.
The Center for the Biology of Chronic Disease (CBCD, http://www.cbcd.net) is a research center recognized by the IRS as a 501(c)(3) non-for-profit organization. The mission of the CBCD is to advance the research on the biology of chronic diseases, and to accelerate the discovery of treatments.
The CBCD published the “Purple” book by Dr. Hanan Polansky. The book presents Dr. Polansky’s highly acclaimed scientific theory on the relationship between foreign DNA and the onset of chronic diseases. Dr. Polansky’s book is available as a free download from the CBCD website.